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Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and upregulation of IL-1Ra in melanoma model

Song, Ju Kyoung ; Park, Mi Hee ; Choi, Dong-Young ; Yoo, Hwan Soo ; Han, Sang Bae ; Yoon, Do Young ; Hong, Jin Tae Li, Jun

PloS one, 2012-05, Vol.7 (5), p.e33747-e33747 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and upregulation of IL-1Ra in melanoma model
Autor: Song, Ju Kyoung ; Park, Mi Hee ; Choi, Dong-Young ; Yoo, Hwan Soo ; Han, Sang Bae ; Yoon, Do Young ; Hong, Jin Tae
Li, Jun
Assuntos: Adenoviruses ; Animal models ; Animal tissues ; Animals ; Apoptosis ; Apoptosis - genetics ; Apoptosis - physiology ; BAX protein ; Bcl-2 protein ; Binding sites ; Biology ; Blotting, Western ; Breast cancer ; Caspase ; Caspase-3 ; CC chemokine receptors ; CCR5 protein ; CD57 antigen ; CD8 antigen ; Cell death ; Cell growth ; Cell Line, Tumor ; Chemokines ; Chemotherapy ; Cytokines ; Cytotoxicity ; Deactivation ; Deoxyribonucleic acid ; DNA ; Gene expression ; Gene regulation ; Immunohistochemistry ; Inactivation ; Infiltration ; Inhibition ; Interleukin 1 receptor antagonist ; Interleukin 1 Receptor Antagonist Protein - genetics ; Interleukin 1 Receptor Antagonist Protein - metabolism ; Interleukin 1 receptors ; Kinases ; Ligands ; Lymphocytes T ; Lymphoma ; Medical research ; Medicine ; Melanoma ; Melanoma - genetics ; Melanoma - metabolism ; Melanoma - pathology ; Metastases ; Metastasis ; Mice ; Mice, Knockout ; Natural killer cells ; NF- Kappa B protein ; NF-kappa B - genetics ; NF-kappa B - metabolism ; NF-κB protein ; Nuclear transport ; Pharmacy ; Phosphorylation ; Poly(ADP-ribose) polymerase ; Prostate cancer ; Receptors, CCR5 - deficiency ; Receptors, CCR5 - genetics ; Rodents ; Signal transduction ; Skin cancer ; Spleen ; Studies ; Survival ; Transcription ; Transcription factors ; Translocation ; Tumors ; Up-regulation ; Weight reduction
É parte de: PloS one, 2012-05, Vol.7 (5), p.e33747-e33747
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Conceived and designed the experiments: JKS JTH. Performed the experiments: JKS MHP DYC. Analyzed the data: MHP DYC. Contributed reagents/materials/analysis tools: HSY SBH DYY. Wrote the paper: JKS JTH.
Descrição: To evaluate the relevance of C-C chemokine receptor type 5 (CCR5) expression and tumor development, we compared melanoma growth in CCR5 knockout (CCR5(-/-)) mice and wild type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced tumor volume, tumor weight, and increased survival rate when compared to CCR5(+/+) mice. We investigated the activation of NF-κB since it is an implicated transcription factor in the regulation of genes involving cell growth, apoptosis, and tumor growth. Significant inhibition of DNA binding activity of NF-κB, and translocation of p50 and p65 into the nucleus through the inhibition of phosphorylation of IκB was found in the melanoma tissues of CCR5(-/-) mice compared to melanoma tissues of CCR5(+/+) mice. NF-κB target apoptotic protein expression, such as cleaved caspase-3, cleaved PARP, and Bax, was elevated, whereas the survival protein expression levels, such as Bcl-2, C-IAP1, was decreased in the melanoma tissues of CCR5(-/-) mice. Interestingly, we found that the level of IL-1Ra, a tumor growth suppressive cytokine, was significantly elevated in tumor tissue and spleen of CCR5(-/-) mice compared to the level in CCR5(+/+) mice. Moreover, infiltration of CD8(+) cytotoxic T cell and CD57(+) natural killer cells was significantly increased in melanoma tumor and spleen tissue of CCR5(-/-) mice compared to that of CCR5(+/+) mice. Therefore, these results showed that CCR5 deficiency caused apoptotic cell death of melanoma through inhibition of NF-κB and upregulation of IL-1Ra.
Editor: United States: Public Library of Science
Idioma: Inglês

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Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and upregulation of IL-1Ra in melanoma model

Song, Ju Kyoung ; Park, Mi Hee ; Choi, Dong-Young ; Yoo, Hwan Soo ; Han, Sang Bae ; Yoon, Do Young ; Hong, Jin Tae Li, Jun

United States: Public Library of Science

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